NM_001004439.2:c.3137C>A

Variant names:

• chr15-68311031-G-T
• rs372902171
• NM_001004439.2:c.3137C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004439.2(ITGA11):​c.3137C>A​(p.Thr1046Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,607,264 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ITGA11 NM_001004439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

Genes affected

ITGA11 (HGNC:6136): (integrin subunit alpha 11) This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein contains an I domain, is expressed in muscle tissue, dimerizes with beta 1 integrin in vitro, and appears to bind collagen in this form. Therefore, the protein may be involved in attaching muscle tissue to the extracellular matrix. Alternative transcriptional splice variants have been found for this gene, but their biological validity is not determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051722437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA11	NM_001004439.2	c.3137C>A	p.Thr1046Asn	missense_variant	Exon 26 of 30	ENST00000315757.9	NP_001004439.1
ITGA11	XM_011521363.3	c.2930C>A	p.Thr977Asn	missense_variant	Exon 24 of 28		XP_011519665.1
ITGA11	XM_005254228.4	c.2831C>A	p.Thr944Asn	missense_variant	Exon 24 of 28		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA11	ENST00000315757.9	c.3137C>A	p.Thr1046Asn	missense_variant	Exon 26 of 30	1	NM_001004439.2	ENSP00000327290.7
ITGA11	ENST00000423218.6	c.3140C>A	p.Thr1047Asn	missense_variant	Exon 26 of 30	2		ENSP00000403392.2

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000506 AC: 12 AN: 236920 AF XY: 0.0000467

Gnomad AFR exome AF: 0.000797

Gnomad AMR exome AF: 0.0000299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000179 AC: 26 AN: 1454902 Hom.: 0 Cov.: 31 AF XY: 0.0000180 AC XY: 13 AN XY: 722940

African (AFR) AF: 0.000600 AC: 20 AN: 33338

American (AMR) AF: 0.0000455 AC: 2 AN: 43968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.00 AC: 0 AN: 84634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108780

Other (OTH) AF: 0.0000499 AC: 3 AN: 60104

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152362 Hom.: 1 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74496

African (AFR) AF: 0.000794 AC: 33 AN: 41582

American (AMR) AF: 0.0000653 AC: 1 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000104 Hom.: 0

Bravo AF: 0.000310

ESP6500AA AF: 0.000482 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000579 AC: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3137C>A (p.T1046N) alteration is located in exon 26 (coding exon 26) of the ITGA11 gene. This alteration results from a C to A substitution at nucleotide position 3137, causing the threonine (T) at amino acid position 1046 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;L
PhyloP100		2.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.058
Sift	Benign	0.55	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.055	.;B
Vest4		0.25
MVP		0.48
MPC		0.13
ClinPred		0.014	T
GERP RS		2.8
Varity_R		0.033
gMVP		0.30
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs372902171; hg19: chr15-68603369;